1. Field of the Invention
The present invention relates to a process for preparing 2-substituted or unsubstituted geranyl acetic acids or esters thereof which are especially useful as pharmaceuticals in the treatment or prophylaxis of dermatosis, such as acne, psoriasis, decubital ulcers or verruca. (See, e.g., British Pat. No. 1,173,419 and Japanese Patent Publication No. 49-43917 corresponding to U.S. patent application Ser. No. 271,687, filed July 14, 1972 now abandoned).
2. Description of the Prior Art
2-SUBSTITUTED GERANYL ACETIC ACIDS OR ESTERS HAVE HERETOFORE BEEN PREPARED BY THE FOLLOWING PROCESSES.
(1) 2-cyclohexyl geranyl acetic acid by the combination of the steps of reacting citral with ethyl cyanoacetate to give the condensation product, reducing the condensation product with sodium borohydride to give ethyl geranyl cyanoacetate, alkylating the geranyl cyanoacetate with cyclohexyl bromide in the presence of alkali and then subjecting said product to hydrolysis with alkali, such as potassium hydroxide, decarboxylation and neutralization to give the product. PA1 (2) A process for preparing 2-cyclohexyl geranyl acetic acid by the combination of the steps of reacting cyclohexanone with ethyl cyanoacetate to give the condensation product, reducing said product with sodium borohydride to give ethyl cyclohexyl cyanoacetate, reacting said ethyl cyclohexyl cyanoacetate with geranyl chloride and then subjecting the product thus obtained to hydrolysis, decarboxylation and neutralization to give the product. PA1 (3) 2-cyclohexyl geranyl acetic acid has also been prepared by reacting cyclohexyl bromide or geranyl chloride with ethyl cyanoacetate to give the condensation product, reacting further cyclohexyl bromide or geranyl chloride with the condensation product, and then subjecting the product thus obtained, to hydrolysis, decarboxylation and neutralization to give the product. PA1 (4) A process for preparing 2-substituted geranyl acetic acid (2-substituted- 5,9-dimethyl-4,8-decadienoic acid), for example, 2-cyclohexyl geranyl acetic acid by reacting linalool with substituted malonic ester, for example, cyclohexyl malonic ester with heating to give the ester of 2-substituted geranyl acetic acid and saponifying the ester with alkali to give the product.
The foregoing methods suffer from the disadvantages inherent in a multistage process and the fact that low yields of the desired product are obtained.